denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Hematology Disease Topics & Pathways:
Hemoglobinopathies, Diseases, Biological Processes
Description:
The purpose of this session is to provide an overview of the available data to support the approach of pyruvate kinase (PK) activation for the treatment of hereditary hemolytic anemias. Red cells rely on glycolysis for ATP production which is critical for maintenance of the red cell shape and survival. A deficiency in ATP leads to hemolytic anemia and ineffective erythropoiesis which is exemplified by the red cell glycolytic enzyme disorders. PK activation has been shown to improve hemolytic anemia, hematopoiesis, and transfusion requirements in adults with PK deficiency. Other hemolytic anemias, such as the thalassemias and sickle cell disease, result in a state of ATP depletion; limitations in ATP may contribute to poor red cell fitness and survival leading to the associated complications of these disorders. Increasing hemoglobin-oxygen affinity with PK activation through a reduction in 2,3-bisphophoglycerate may decrease red cell sickling, in addition to improving red cell survival, in sickle cell disease. By increasing red cell energy, PK activators may be efficacious across a broad range of hemolytic anemias. This educational session will explore the evidence for consideration of PK activators as a treatment for PK deficiency, sickle cell disease, and the thalassemias, among other red cell disorders.
Dr. Rachael Grace will review the phase 2 and 3 trial data of PK activators for the treatment of adults with pyruvate kinase deficiency. Given that an accurate diagnosis is critical to allow the opportunity for disease-directed treatments, she will discuss the clinical presentation and diagnostic evaluation in children and adults with PK deficiency. This talk will outline real world decision-making for treatment of PK deficiency with PK activators and other treatment options including supportive approaches of transfusions and splenectomy as well as hematopoietic stem cell transplant and clinical trials of gene therapy.
Dr. Dr. van Beers will discuss the consequences of chronic anemia in sickle cell disease and currently available treatment options. He will describe the therapeutic mechanisms of action of PK activators that may improve anemia, reduce hemolysis, and reduce HbS polymerization and sickling in sickle cell disease. This talk will review the existing evidence as well as additional considerations for the use of PK activators in the treatment of sickle cell disease.
Dr. Kevin Kuo will outline current challenges in the management of thalassemia. He will review preclinical data of PK activation in thalassemia and the mechanism by which this may lead to improvement of anemia in patients with thalassemia. Dr. Kuo will discuss existing evidence of the efficacy and safety of PK activators in thalassemia and considerations of which patients should be considered for clinical trials.
Dr. Rachael Grace will review the phase 2 and 3 trial data of PK activators for the treatment of adults with pyruvate kinase deficiency. Given that an accurate diagnosis is critical to allow the opportunity for disease-directed treatments, she will discuss the clinical presentation and diagnostic evaluation in children and adults with PK deficiency. This talk will outline real world decision-making for treatment of PK deficiency with PK activators and other treatment options including supportive approaches of transfusions and splenectomy as well as hematopoietic stem cell transplant and clinical trials of gene therapy.
Dr. Dr. van Beers will discuss the consequences of chronic anemia in sickle cell disease and currently available treatment options. He will describe the therapeutic mechanisms of action of PK activators that may improve anemia, reduce hemolysis, and reduce HbS polymerization and sickling in sickle cell disease. This talk will review the existing evidence as well as additional considerations for the use of PK activators in the treatment of sickle cell disease.
Dr. Kevin Kuo will outline current challenges in the management of thalassemia. He will review preclinical data of PK activation in thalassemia and the mechanism by which this may lead to improvement of anemia in patients with thalassemia. Dr. Kuo will discuss existing evidence of the efficacy and safety of PK activators in thalassemia and considerations of which patients should be considered for clinical trials.